The causes of schizophrenia have been the subject of much debate, with various factors proposed and discounted or modified. The language of schizophrenia research under the medical model is scientific. Such studies suggest that genetics, prenatal development, early environment, neurobiology and psychological and social processes are important contributory factors.

Current psychiatric research into the development of the disorder is often based on a neurodevelopmental model (proponents of which see schizophrenia as a syndrome.[1][2]) However,
schizophrenia is diagnosed on the basis of symptom profiles. Neural correlates do not provide sufficiently useful criteria.[3] "Current research into schizophrenia has remained highly fragmented, much like the clinical presentation of the disease itself".[4]

Although no common cause of schizophrenia has been identified in all individuals diagnosed with the condition, currently most researchers and clinicians believe it results from a combination of both brain vulnerabilities (either inherited or acquired) and life events. This widely adopted approach is known as the 'stress-vulnerability' model,[5] and much scientific debate now focuses on how much each of these factors contributes to the development and maintenance of schizophrenia.

Schizophrenia is most commonly first diagnosed during late adolescence or early adulthood, suggesting it is often the end process of childhood and adolescent development. There is on average a somewhat earlier onset for men than women, with the possible influence of the female hormone estrogen being one hypothesis and sociocultural influences another.[6]

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Evidence suggests that genetic vulnerability and environmental factors can act in combination to result in diagnosis of schizophrenia.[7] Research suggests that genetic vulnerability to schizophrenia is multifactorial, caused by interactions of several genes.[8]

Both individual twin studies and meta-analyses of twin studies estimate the heritability of risk for schizophrenia to be approximately 80% (this refers to the proportion of variation between individuals in a population that is influenced by genetic factors, not the degree of genetic determination of individual risk). Concordance rates between monozygotic twins was close to 50%; whereas dizygotic twins was 17%. Adoption studies have also indicated a somewhat increased risk in those with a parent with schizophrenia even when raised apart. Studies suggest that the phenotype is genetically influenced but not genetically determined; that the variants in genes are generally within the range of normal human variation and have low risk associated with them each individually; and that some interact with each other and with environmental risk factors; and that they may not be specific to schizophrenia.[9]

Some twin studies[10][11] have found rates as low as 11.0%–13.8% among monozygotic twins, and 1.8%–4.1% among dizygotic twins, however.
Tyronne Cannon reviewed the situation, stating: "Previous twin studies have reported estimates of broad heritability ranging from 0.41 to 0.87"[12] Yet, in the "Pairs of Veteran Twins" study, for example, 338 pairs were schizophrenic with only 26 pairs concordant, and it was concluded in one report: "the role of the suggested genetic factor appears to be a limited one; 85 percent of the affected monozygotic pairs in the sample were discordant for schizophrenia".[13] In addition, some scientists criticize the methodology of the twin studies, and have argued that the genetic basis of schizophrenia is still largely unknown or open to different interpretations.[9]
For example, although the concordance of schizophrenia occurrence in monozygotic twins has traditionally been used to estimate a genetic component to the illness, the results could be skewed because of environmental factors like a shared placenta[14][15][16]

In fact, researchers, have used the phenomenon of 'fetal programming' to account for familial patterns in epidemiological studies. "Intra-uterine growth is a complex outcome that is influenced by a wide range of factors including fetal genotype, maternal physiology and behaviour as well as the function of that crucial interface—the placenta," said one journal.[17]

After reviewing techniques like: Genome Wide Association Studies; Single Nucleotide Polymorphisms and Copy Number Variations; the Nature journal reports: the basic observation is that, "You have this clear tangible phenomenon in which children resemble their parents"...."Despite what children get told in elementary school science we just don't know how that works," as Professor of ecology and evolutionary biology at Princeton, Leonid Kruglyak, says (in reviewing hereditibility in general).[18] It cites schizophrenia as a trait in which the genes have gone missing.

A great deal of effort has been put into molecular genetic studies of schizophrenia, which attempt to identify specific genes which may increase risk. A 2003 review of linkage studies listed seven genes as likely to increase risk for a later diagnosis of the disorder.[7] Two recent reviews[8][9] suggested that the evidence was strongest for two genes known as dysbindin (DTNBP1) and neuregulin (NRG1), and that a number of other genes (such as COMT, RGS4, PPP3CC, ZDHHC8, DISC1, and AKT1) showed some early promising results. Variations near the gene FXYD6 have also been associated with schizophrenia in the UK[19][20] but not in Japan.[21] In 2008, rs7341475SNP of the reelin gene was associated with an increased risk of schizophrenia in women, but not in men. This female-specific association was replicated in several populations.[22] Still another review found evidence that the protein phosphatase 2B (calcineurin) might be involved in susceptibility to schizophrenia.[3]

The largest most comprehensive genetic study of its kind, involving tests of several hundred single nucleotide polymorphisms (SNPs) in nearly 1,900 individuals with schizophrenia or schizoaffective disorder and 2,000 comparison subjects, reported in 2008 that there was no evidence of any significant association between the disorders and any of 14 previously identified candidate genes (RGS4, DISC1, DTNBP1, STX7, TAAR6,
PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1,
CHRNA7, COMT, and ARVCF). The statistical distributions suggested nothing more than chance variation. The authors concluded that the findings make it unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects could not be ruled out.[23]

Other research has suggested that a greater than average number of rare deletions or duplications of tiny DNA sequences within genes (known as copy number variants) are linked to increased risk for schizophrenia, especially in those "sporadic" cases not linked to family history of schizophrenia, and that the genetic factors and developmental pathways can thus be different in different individuals.[25][26] A genome wide survey of 3,391 individuals with schizophrenia found CNVs in less than 1% of cases. Within them, deletions in regions related to psychosis were observed, as well as deletions on chromosome 15q13.3 and 1q21.1.[27]

CNVs occur due to non-allelic homologous recombination mediated by low copy repeats (sequentially similar regions). This results in deletions and duplications of dosage sensitive genes. It has been speculated that CNVs underlie a significant proportion of normal human variation, including differences in cognitive, behavioral, and psychological features, and that CNVs in at least three loci can result in increased risk for schizophrenia in a few individuals.[28]Epigenetics may also play a role in schizophrenia, with the expression of Protocadherin 11 X/Protocadherin Y playing a possible role in schizophrenia.[29]

A 2009 study was able to create mice matching schizophrenic symptoms by the deletion of only one gene set, those of the neuregulin post-synaptic receptor. The result showed that although the mice mostly developed normally, on further brain development, glutamate receptors brokedown. This theory supports the glutamate hypothesis of schizophrenia.[30]
Another study in 2009 by Simon Fraser University researchers identifies a link between Autism and Schizophrenia :health

"The SFU group found that variations in four sets of genes are related to both autism and schizophrenia. People normally have two copies of each gene, but in autistics some genome locations have only single copies and in schizophrenics extra copies are present at the same locations." "Source"

Schizophrenia has been considered an evolutionary puzzle due to the combination of high heritability, relatively high prevalence, and reduced reproductive success. One explanation could be increased reproductive success by close relatives without symptoms but this does not seem to be the case. Still, it has been argued that it is possible that a low amount of schizotypy increasing genes may increase reproductive success by increasing such traits such as creativity, verbal ability, and emotional sensitivity.[31]

Another evolutionary explanations is the "imprinted brain theory" which argues that psychosis and autism are contrasting disorders on a number of different variables. This is argued to be caused by an unbalanced genomic imprinting favoring paternal genes in the case of autism and maternal genes in the case of psychosis.[32]

It is well established that obstetric complications or events are associated with an increased chance of the child later developing schizophrenia, although overall they constitute a non-specific risk factor with a relatively small effect. Obstetric complications occur in approximately 25 to 30% of the general population and the vast majority do not develop schizophrenia, and likewise the majority of individuals with schizophrenia have not had a detectable obstetric event. Nevertheless, the increased average risk is well-replicated, and such events may moderate the effects of genetic or other environmental risk factors. The specific complications or events most linked to schizophrenia, and the mechanisms of their effects, are still under examination.[33]

One epidemiological finding is that people diagnosed with schizophrenia are more likely to have been born in winter or spring[34] (at least in the northern hemisphere). However, the effect is not large. Explanations have included a greater prevalence of viral infections at that time, or a greater likelihood of vitamin D deficiency. A similar effect (increased likelihood of being born in winter and spring) has also been found with other, healthy populations, such as chess players.[35]

Women who were pregnant during the Dutch famine of 1944, where many people were close to starvation (experiencing malnutrition) had a higher chance of having a child who would later develop schizophrenia.[36] Studies of Finnish mothers who were pregnant when they found out that their husbands had been killed during the Winter War of 1939–1940 have shown that their children were significantly more likely to develop schizophrenia when compared with mothers who found out about their husbands' death after pregnancy, suggesting that maternal stress may have an effect.[37]

Lower than average birth weight has been one of the most consistent findings, indicating slowed fetal growth possibly mediated by genetic effects. Almost any factor adversely affecting the fetus will affect growth rate, however, so the association has been described as not particularly informative regarding causation.[33] In addition, the majority of birth cohort studies have failed to find a link between schizophrenia and low birth weight or other signs of growth retardation.[38]

Animal models have suggested links between intrauterine growth restriction and specific neurological abnormalities similar to those that may be involved in the development of schizophrenia, including ventricular enlargement and reduced hippocampal volume in guinea pigs.[39]

It has been hypothesized since the 1970s that brain hypoxia (low oxygen levels) before, at or immediately after birth may be a risk factor for the development of schizophrenia.[40][41]

Hypoxia is now being demonstrated as relevant to schizophrenia in animal models, molecular biology and epidemiology studies. One study in Molecular Psychiatry was able to differentiate 90% of schizophrenics from controls based on hypoxia and metabolism.[42] Hypoxia has been recently described as one of the most important of the external factors that influence susceptibility, although studies have been mainly epidemiological. Such studies place a high degree of importance on hypoxic influence, but because of familial pattern of the illness in some families, propose a genetic factor also; stopping short of concluding hypoxia to be the sole cause.[43] Fetal hypoxia, in the presence of certain unidentified genes, has been correlated with reduced volume of the hippocampus, which is in turn correlated with schizophrenia.[44]

Although most studies have interpreted hypoxia as causing some form of neuronal dysfunction or even subtle damage, it has been suggested that the physiological hypoxia that prevails in normal embryonic and fetal development, or pathological hypoxia or ischemia, may exert an effect by regulating or dysregulating genes involved in neurodevelopment. A literature review judged that over 50% of the candidate genes for susceptibility to schizophrenia met criteria for "ischemia–hypoxia regulation and/or vascular expression" even though only 3.5% of all genes were estimated to be involved in hypoxia/ischemia or the vasculature.[45]

A longitudinal study found that obstetric complications involving hypoxia were one factor associated with neurodevelopmental impairments in childhood and with the later development of schizophreniform disorders.[46] Fetal hypoxia has been found to predict unusual movements at age 4 (but not age 7) among children who go on to develop schizophrenia, suggesting that its effects are specific to the stage of neurodevelopment.[47] A Japanese case study of monozygotic twins discordant for schizophrenia (one has the diagnosis while the other does not) draws attention to their different weights at birth and concludes hypoxia may be the differentiating factor.[48]

The unusual functional laterality in speech production (e.g. right hemisphere auditory processing) found in some individuals with schizophrenia could be due to aberrant neural networks established as a compensation for left temporal lobe damage induced by pre- or perinatal hypoxia.[49] Prenatal and perinatal hypoxia appears to be important as one factor in the neurodevelopmental model, with the important implication that some forms of schizophrenia may thus be preventable.[50]

Research on rodents seeking to understand the possible role of prenatal hypoxia in disorders such as schizophrenia has indicated that it can lead to a range of sensorimotor and learning/memory abnormalities. Impairments in motor function and coordination, evident on challenging tasks when the hypoxia was severe enough to cause brain damage, were long-lasting and described as a "hallmark of prenatal hypoxia".[51][52]

Several animal studies have indicated that fetal hypoxia can affect many of the same neural substrates implicated in schizophrenia, depending on the severity and duration of the hypoxic event as well as the period of gestation, and in humans moderate or severe (but not mild) fetal hypoxia has been linked to a series of motor, language and cognitive deficits in children, regardless of genetic liability to schizophrenia.[53] One paper restated that cerebellum neurological disorders were frequently found in schizophrenics and speculated hypoxia may cause the subsequent cognitive dysmetria[54]

Whereas most studies find only a modest effect of hypoxia in schizophrenia, a longitudinal study using a combination of indicators to detect possible fetal hypoxia, such as early equivalents of Neurological Soft Signs or obstetric complications, reported that the risk of schizophrenia and other nonaffective psychoses was "strikingly elevated" (5.75% versus 0.39%). Although objective estimates of hypoxia did not account for all schizophrenic cases; the study revealed increasing odds of schizophrenia according to graded increase in severity of hypoxia.[55]

There is an emerging literature on a wide range of prenatal risk factors, such as prenatal stress, intrauterine (in the womb) malnutrition, and prenatal infection. Increased paternal age has been linked to schizophrenia, possibly due to "chromosomal aberrations and mutations of the aging germline."[56] Maternal-fetal rhesus or genotype incompatibility has also been linked, via increasing the risk of an adverse prenatal environment. Also, in mothers with schizophrenia, an increased risk has been identified via a complex interaction between maternal genotype, maternal behavior, prenatal environment and possibly medication and socioeconomic factors.[33] References for many of these environmental risk factors have been collected in an online database.[57]

There may be an association between celiac disease (gluten intolerance) and schizophrenia in a small proportion of patients, though large randomized controlled trials and epidemiological studies will be needed before such an association can be confirmed. Withdrawal of gluten from the diet is an inexpensive measure which may improve the symptoms in a small (≤3%) number of schizophrenic patients.[58]

In addition, there is some evidence that exposure to toxins such as lead can also increase the risk of later development of schizophrenia spectrum disorders.[59]

Numerous viral infections, in utero or in childhood, have been associated with an increased risk of later developing schizophrenia.[60] Schizophrenia is somewhat more common in those born in winter to early spring, when infections are more common.[61]

Influenza has long been studied as a possible factor. A 1988 study found that individuals who were exposed to the Asian flu as second trimester fetuses were at increased risk of eventually developing schizophrenia.[62] This result was corroborated by a later British study of the same pandemic,[63] but not by a 1994 study of the pandemic in Croatia.[64] A Japanese study also found no support for a link between schizophrenia and birth after an influenza epidemic.[65]

In a meta-analysis of several studies, they found moderately higher levels of Toxoplasma antibodies in those with schizophrenia[68][69] and possibly higher rates of prenatal or early postnatal exposure to Toxoplasma gondii, but not acute infection. However, in another study of postmortem brain tissue, the authors have reported equivocal or negative results, including no evidence of herpes virus or T. gondii involvement in schizophrenia.[70]

There is some evidence for the role of autoimmunity in the development of some cases of schizophrenia. A statistical correlation has been reported with various autoimmune diseases[71] and direct studies have linked dysfunctional immune status to some of the clinical features of schizophrenia.[72][73]

This is known as the pathogenic theory of schizophrenia or germ theory of schizophrenia. It is a pathogenic theory of disease in which it is thought that a proximal cause of certain cases of schizophrenia is the interaction of the developing fetus with pathogens such as viruses, or with antibodies from the mother created in response to these pathogens (in particular, Interleukin 8).[74] Substantial research suggests that exposure to certain illnesses (e.g., influenza) in the mother of the neonate (especially at the end of the second trimester) causes defects in neural development which may emerge as a predisposition to schizophrenia around the time of puberty, as the brain grows and develops.[75]

In general, the antecedents of schizophrenia are subtle and those who will go on to develop schizophrenia do not form a readily identifiable subgroup - which would lead to identification of a specific cause. Average group differences from the norm may be in the direction of superior as well as inferior performance. Overall, birth cohort studies have indicated subtle nonspecific behavioral features, some evidence for psychotic-like experiences (particularly hallucinations), and various cognitive antecedents. There have been some inconsistencies in the particular domains of functioning identified and whether they continue through childhood and whether they are specific to schizophrenia.[38]

A prospective study found average differences across a range of developmental domains, including reaching milestones of motor development at a later age, having more speech problems, lower educational test results, solitary play preferences at ages four and six, and being more socially anxious at age 13. Lower ratings of the mother's skills and understanding of the child at age 4 were also related.[76]

Some of the early developmental differences were identified in the first year of life in a study in Finland, although generally related to psychotic disorders rather than schizophrenia in particular.[77] The early subtle motor signs persisted to some extent, showing a small link to later school performance in adolescence.[78] An earlier Finnish study found that childhood performance of 400 individuals diagnosed with schizophrenia was significantly worse than controls on subjects involving motor co-ordination (sports and handcrafts) between ages 7 and 9, but there were no differences on academic subjects (contrary to some other IQ findings).[79] (Patients in this age group with these symptoms were significantly less likely to progress to high school, despite academic ability[80])

However, reanalysis of the data from the later Finnish study, on older children (14 to 16) in a changed school system, using narrower diagnostic criteria and with less cases but more controls, did not support a significant difference on sports and handicraft performance.[81] However, another study found that unusual motor coordination scores at 7 years of age were associated in adulthood with both those with schizophrenia and their unaffected siblings, while unusual movements at ages 4 and 7 predicted adult schizophrenia but not unaffected sibling status.[47]

A birth cohort study in New Zealand found that children who went on to develop schizophreniform disorder had, as well as emotional problems and interpersonal difficulties linked to all adult psychiatric outcomes measured, significant impairments in neuromotor, receptive language, and cognitive development.[46] A retrospective study found that adults with schizophrenia had performed better than average in artistic subjects at ages 12 and 15, and in linguistic and religious subjects at age 12, but worse than average in gymnastics at age 15.[82]

Some small studies on offspring of individuals with schizophrenia have identified various neurobehavioral deficits,[83] a poorer family environment and disruptive school behaviour,[84] poor peer engagement, immaturity or unpopularity[85] or poorer social competence and increasing schizophrenic symptomology emerging during adolescence.[86]

A minority "deficit syndrome" subtype of schizophrenia is proposed to be more marked by early poor adjustment and behavioral problems, as compared to non-deficit subtypes.[87]

The relationship between schizophrenia and drug use is complex, meaning that a clear causal connection between drug use and schizophrenia has been difficult to tease apart. There is strong evidence that using certain drugs can trigger either the onset or relapse of schizophrenia in some people. It may also be the case, however, that people with schizophrenia use drugs to overcome negative feelings associated with both the commonly prescribed antipsychotic medication and the condition itself, where negative emotion, paranoia and anhedonia are all considered to be core features.

The rate of substance use is known to be particularly high in this group. In a recent study, 60% of people with schizophrenia were found to use substances and 37% would be diagnosable with a substance use disorder.[88]

There is some evidence that cannabis use can contribute to schizophrenia. Some studies suggest that cannabis is neither a sufficient nor necessary factor in developing schizophrenia, but that cannabis may significantly increase the risk of developing schizophrenia and may be, among other things, a significant causal factor. Nevertheless, some previous research in this area has been criticised as it has often not been clear whether cannabis use is a cause or effect of schizophrenia. To address this issue, a recent review of studies from which a causal contribution to schizophrenia can be assessed has suggested that cannabis statistically doubles the risk of developing schizophrenia on the individual level, and may, assuming a causal relationship, be responsible for up to 8% of cases in the population.[89]

An older longitudinal study, published in 1987, suggested a sixfold increase of schizophrenia risks for high consumers of cannabis (use on more than fifty occasions) in Sweden.[90]

Despite increases in cannabis consumption in the 1960s and 1970s in western society, rates of psychotic disorders such as schizophrenia remained relatively stable over time.[91][92][93]
Also, Sweden and Japan, where self-reported marijuana use is very low, do not have lower rates of psychosis than the U.S. and Canada do.[94] Thus, there remains controversy over whether or not the apparent association between cannabis and schizophrenia is a causal relationship.

As amphetamines trigger the release of dopamine and excessive dopamine function is believed to be responsible for many symptoms of schizophrenia (known as the dopamine hypothesis of schizophrenia), amphetamines may worsen schizophrenia symptoms.[95] In addition, amphetamines are known to cause a stimulant psychosis in otherwise healthy individuals that superficially resembles schizophrenia, and may be misdiagnosed as such by some healthcare professionals.

Drugs such as ketamine, PCP, and LSD have been used to mimic schizophrenia for research purposes. Using LSD and other psychedelics as a model has now fallen out of favor with the scientific research community, as the differences between the drug induced states and the typical presentation of schizophrenia have become clear. The dissociatives ketamine and PCP, however, are still considered to produce states that are remarkably similar however, and are considered to be even better models than stimulants since they produce both positive and negative symptoms.

People with schizophrenia tend to smoke significantly more tobacco than the general population. The rates are exceptionally high amongst institutionalized patients and homeless people. In a UK census from 1993, 74% of people with schizophrenia living in institutions were found to be smokers.[96][97] A 1999 study that covered all people with schizophrenia in Nithsdale, Scotland found a 58% prevalence rate of cigarette smoking, to compare with 28% in the general population.[98] An older study found that as much as 88% of outpatients with schizophrenia were smokers.[99]

Despite the higher prevalence of tobacco smoking, people diagnosed with schizophrenia have a much lower than average chance of developing and dying from lung cancer. While the reason for this is unknown, it may be because of a genetic resistance to the cancer, a side effect of drugs being taken, or a statistical effect of increased likelihood of dying from causes other than lung cancer.[100]

A 2003 study of over 50,000 Swedish conscripts found that there was a small but significant protective effect of smoking cigarettes on the risk of developing schizophrenia later in life.[101] While the authors of the study stressed that the risks of smoking far outweigh these minor benefits, this study provides further evidence for the 'self-medication' theory of smoking in schizophrenia and may give clues as to how schizophrenia might develop at the molecular level. Furthermore, many people with schizophrenia have smoked tobacco products long before they are diagnosed with the illness, and a cohort study of Israeli conscripts found that healthy adolescent smokers were more likely to develop schizophrenia in the future than their nonsmoking peers.[102]

It is of interest that cigarette smoking affects liver function such that the antipsychotic drugs used to treat schizophrenia are broken down in the blood stream more quickly. This means that smokers with schizophrenia need slightly higher doses of antipsychotic drugs in order for them to be effective than do their non-smoking counterparts.[citation needed]

The increased rate of smoking in schizophrenia may be due to a desire to self-medicate with nicotine. One possible reason is that smoking produces a short term effect to improve alertness and cognitive functioning in persons who suffer this illness.[103] It has been postulated that the mechanism of this effect is that people with schizophrenia have a disturbance of nicotinic receptor functioning which is temporarily abated by tobacco use.[103] However, some researchers have questioned whether self-medication is really the best explanation for the association.[104]

A study from 1989[105] and a 2004 case study[106] show that when haloperidol is administered, nicotine limits the extent to which the antipsychotic increases the sensitivity of the dopamine 2 receptor. Dependent on the dopamine system, symptoms of Tardive Dyskinesia are not found in the nicotine administered patients despite a roughly 70% increase in dopamine receptor activity, but the controls have more than 90% and do develop symptoms.A 1997 study showed that akathisia was significantly reduced upon administration of nicotine when the akathisia was induced by antipsychotics.[107] This gives credence to the idea tobacco could be used to self medicate by limiting effects of the illness, the medication, or both.

The chance of developing schizophrenia has been found to increase with the number of adverse social factors (e.g. indicators of socioeconomic disadvantage or social exclusion) present in childhood.[108][109] Stressful life events generally precede the onset of schizophrenia.[110] A personal or recent family history of migration is a considerable risk factor for schizophrenia, which has been linked to psychosocial adversity, social defeat from being an outsider, racial discrimination, family dysfunction, unemployment and poor housing conditions.[111][112] Unemployment and early separation from parents are some important factors which are responsible for the higher rates of schizophrenia among British African Caribbean, in comparison to native African Caribbean. This is an example which shows that social disadvantage plays an equally major hand in onset schizophrenia as genetics.[113]

Childhood experiences of abuse or trauma are risk factors for a diagnosis of schizophrenia later in life.[114][115][116][117] Recent large-scale general population studies indicate the relationship is a causal one, with an increasing risk with additional experiences of maltreatment,[118] although a critical review suggests conceptual and methodological issues require further research.[119] There is some evidence that adversities may lead to cognitive biases and/or altered dopamine neurotransmission, a process that has been termed "sensitization".[120]

Specific social experiences have been linked to specific psychological mechanisms and psychotic experiences in schizophrenia. In addition, structural neuroimaging studies of victims of sexual abuse and other traumas have sometimes reported findings similar to those sometimes found in psychotic patients, such as thinning of the corpus callosum, loss of volume in the anterior cingulate cortex, and reduced hippocampal volume.[121]

A particularly stable and replicable finding has been the association between living in an urban environment and the development of schizophrenia, even after factors such as drug use, ethnic group and size of social group have been controlled for.[122] A recent study of 4.4 million men and women in Sweden found a 68%–77% increased risk of diagnosed psychosis for people living in the most urbanized environments, a significant proportion of which is likely to be described as schizophrenia.[123]

The effect does not appear to be due to a higher incidence of obstetric complications in urban environments.[124] The risk increases with the number of years and degree of urban living in childhood and adolescence, suggesting that constant, cumulative, or repeated exposures during upbringing occurring more frequently in urbanized areas are responsible for the association.[125]

Various possible explanations for the effect have been judged unlikely based on the nature of the findings, including infectious causes or a generic stress effect. It is thought to interact with genetic dispositions and, since there appears to be nonrandom variation even across different neighborhoods, and an independent association with social isolation, it has been proposed that the degree of "social capital" (e.g. degree of mutual trust, bonding and safety in neighborhoods) can exert a developmental impact on children growing up in these environments.[126]

Evidence is consistent that negative attitudes from others increase the risk of schizophrenia relapse, in particular critical comments, hostility, authoritarian, and intrusive or controlling attitudes (termed 'high expressed emotion' by researchers).[127] Although family members and significant others are not held responsible for schizophrenia - the attitudes, behaviors and interactions of all parties are addressed - unsupportive dysfunctional relationships may also contribute to an increased risk of developing schizophrenia.[128][129] Social support systems are very important for schizophrenics and the people with whom they are in relationships.[130]

Psychiatrists R. D. Laing, Silvano Arieti, Theodore Lidz and others have argued that the symptoms of what is called mental illness are comprehensible reactions to impossible demands that society and particularly family life places on some sensitive individuals. Laing, Arieti and Lidz were notable in valuing the content of psychotic experience as worthy of interpretation, rather than considering it simply as a secondary and essentially meaningless marker of underlying psychological or neurological distress. Laing described eleven case studies of people diagnosed with schizophrenia and argued that the content of their actions and statements was meaningful and logical in the context of their family and life situations.[131]

In 1956, Gregory Bateson and his colleagues Paul Watzlawick, Donald Jackson, and Jay Haley[132] articulated a theory of schizophrenia, related to Laing's work, as stemming from double bind situations where a person receives different or contradictory messages. Madness was therefore an expression of this distress and should be valued as a cathartic and transformative experience. In the books Schizophrenia and the Family and The Origin and Treatment of Schizophrenic Disorders Lidz and his colleagues explain their belief that parental behaviour can result in mental illness in children. Arieti's Interpretation of Schizophrenia won the 1975 scientific National Book Award in the United States.

The concept of schizophrenia as a result of civilization has been developed further by psychologist Julian Jaynes in his 1976 book The Origin of Consciousness in the Breakdown of the Bicameral Mind; he proposed that until the beginning of historic times, schizophrenia or a similar condition was the normal state of human consciousness.[133] This would take the form of a "bicameral mind" where a normal state of low affect, suitable for routine activities, would be interrupted in moments of crisis by "mysterious voices" giving instructions, which early people characterized as interventions from the gods. Researchers into shamanism have speculated that in some cultures schizophrenia or related conditions may predispose an individual to becoming a shaman;[134] the experience of having access to multiple realities is not uncommon in schizophrenia, and is a core experience in many shamanic traditions. Equally, the shaman may have the skill to bring on and direct some of the altered states of consciousness psychiatrists label as illness. Psychohistorians, on the other hand, accept the psychiatric diagnoses. However, unlike the current medical model of mental disorders they may argue that poor parenting in tribal societies causes the shaman's schizoid personalities.[135] Commentators such as Paul Kurtz and others have endorsed the idea that major religious figures experienced psychosis, heard voices and displayed delusions of grandeur.[136]

Modern clinical psychological research has indicated a number of processes which may cause or bring on episodes of schizophrenia.

A number of cognitive biases and deficits have been identified. These include attribution biases in social situations, difficulty distinguishing inner speech from speech from an external source (source monitoring), difficulty in adjusting speech to the needs of the hearer, difficulties in the very earliest stages of processing visual information (including reduced latent inhibition), and an attentional bias towards threats.

Some of these tendencies have been shown to worsen or appear when under emotional stress or in confusing situations. As with related neurological findings, they are not shown by all individuals with a diagnosis of schizophrenia, and it is not clear how specific they are to schizophrenia.[137] However, the findings regarding cognitive difficulties in schizophrenia are reliable and consistent enough for some researchers to argue that they are diagnostic.[138]

Impaired capacity to appreciate one's own and others' mental states has been reported to be the single-best predictor of poor social competence in schizophrenia,[139] and similar cognitive features have been identified in close relatives of people diagnosed with schizophrenia.[140]

A number of emotional factors have been implicated in schizophrenia, with some models putting them at the core of the disorder. It was thought that the appearance of blunted affect meant that sufferers did not experience strong emotions, but more recent studies indicate there is often a normal or even heightened level of emotionality, particularly in response to negative events or stressful social situations.[141] Some theories suggest positive symptoms of schizophrenia can result from or be worsened by negative emotions, including depressed feelings and low self-esteem[142] and feelings of vulnerability, inferiority or loneliness.[143] Chronic negative feelings and maladaptive coping skills may explain some of the association between psychosocial stressors and symptomology.[144] Critical and controlling behaviour by significant others (high expressed emotion) causes increased emotional arousal[145] and lowered self-esteem[146] and a subsequent increase in positive symptoms such as unusual thoughts. Countries or cultures where schizotypal personalities or schizophrenia symptoms are more accepted or valued appear to be associated with reduced onset of, or increased recovery from, schizophrenia.

Related studies suggest that the content of delusional and psychotic beliefs in schizophrenia can be meaningful and play a causal or mediating role in reflecting the life history, or social circumstances of the individual.[147] Holding minority socio-cultural beliefs, for example due to ethnic background, has been linked to increased diagnosis of schizophrenia. The way an individual interprets his or her delusions and hallucinations (e.g. as threatening or as potentially positive) has also been found to influence functioning and recovery.[148]

Some experts think autonomy vs intimacy is a motivation for schizophrenic symptoms.[149]

Other lines of work relating to the self in schizophrenia have linked it to psychological dissociation[150] or abnormal states of awareness and identity as understood from phenomenological and other perspectives.[151][152]

Psychiatrist Tim Crow has argued that schizophrenia may be the evolutionary price we pay for a left brain hemisphere specialization for language.[153] Since psychosis is associated with greater levels of right brain hemisphere activation and a reduction in the usual left brain hemisphere dominance, our language abilities may have evolved at the cost of causing schizophrenia when this system breaks down.

In alternative medicine, some practitioners believe that there are a vast number of physical causes of what ends up being diagnosed as schizophrenia.[154] While some of these explanations may stretch credulity, others (such as heavy metal poisoning and nutritional imbalances) have been supported at least somewhat by research.[59][155][156] However, it is not entirely clear how many patients initially diagnosed with schizophrenia these alternative explanations may account for.

↑The above reference is cited in a 2006 work, in giving a history of minimal brain dysfunction saying: "It was also noted that individuals who experienced perinatal brain hypoxia constituted a population at risk for minimal brain dysfunction, and that children attending psychiatric clinics often presented with illnesses or perinatal complications of a sort known to be associated with neurological brain damage (Handford 1975)."Disorganized Children : A Guide for Parents and Professionals Jessica Kingsley Publishers Ltd. Stein, Samuel M.p135